Results:
Baseline patient characteristics are given in Table 1 . Patients
with DMS were older than RMS patients (77 ± 12 vs. 61 ± 15 y, p
< 0.001). Study subjects were predominantly females (80% in
DMS vs. 83% in RMS, p = 0.7). Patients with DMS had a higher prevalence
of hypertension (92% vs. 70% in RMS, p = 0.009) and chronic kidney
disease (53% vs. 29% in RMS, p = 0.045). There was a higher prevalence
of AF in the RMS group (38% vs. 14% in DMS, p = 0.034). Patients with
DMS had a lower mean TMPG (6.0±1.8 vs. 7.9±2.9, p<0.003) and a
larger MVACEQ (1.4±0.4 vs. 0.98±0.3
cm2) despite a similar LVOT SV (in the absence of
significant MR and aortic regurgitation) (Table 2 ). After the
exclusion of patients with ESRD, there were 16 patients in the DMS group
with high LVOT flow defined as LVOT VTI >25 cm. Even after
the exclusion of high LVOT flow, the DMS group still had a larger
MVACEQ (1.3±0.4 vs. 1.0±0.2 cm2, p<0.001) and
lower TMPG (5.6±2 vs. 8±3 mm HG, p=0.001) compared to RMS group.
The average of mean TMPG in all subjects was 6.3 mmHg. Patients with a
TMPG of > 6.3 mmHg (n=39), had a larger
MVACEQ in the DMS group (n=24) than RMS group (n=14)
(1.4±0.4 vs. 0.8±0.2 cm2, p= 0.001) (Figure
3 ). The frequency of low flow state defined as SV index <35
ml/m2 was 41% (n=24) and 43% (n=10) in the DMS and
RMS groups, respectively (p=0.8). TMPG was significantly lower in the
DMS group irrespective of the SV index (Table 2 ).
We stratified the echocardiographic variables by the presence of AF in
the DMS group. No significant in-between group differences (DMS patients
with AF versus without AF) were observed in mean TMPG (mean difference
-0.50 mmHg [-1.9 - 0.90], p = 0.475), LVOT SV (mean difference -7.2
ml [-17.1 - 2.0], p = 0.122), and DMSI (mean difference
0.02 [-0.06 - 0.87], p = 0.705).
We stratified DMS patients by MVACEQ to understand the
association of MS severity with other echocardiographic variables
(Table 3 ). There was a statistically significant gradual
increase in E velocity with worsening MS severity defined by
MVACEQ. However, A velocity and E/A ratio did not
correlate with MS severity. There was a statistically significant
difference in DMSI between all three groups, and it progressively got
smaller with severe stenosis.
DMSI accounted for 79% of the variation in MVACEQ(Table 4, Figure 4A ), whereas the mean TMPG accounted for only
8% of the variation in patients with DMS (Figure 4B ). There
was also no correlation between DMSI and mean TMPG in the DMS group
(Figure 4C ).
The ROC curve showed that a DMSI of ≤ 0.50 was associated with
MVACEQ ≤ 1.5 cm2 (AUROC 0.971, p =
0.001) and DMSI of ≤ 0.351 was associated with MVACEQ ≤
1.0 cm2 (AUROC 0.965, p = 0.0001).
The interclass correlation (performed in 8 patients) for mean TMPG was
0.909 (CI 0.546 – 0.982, p < 0.001), for
MVACEQ was 0.966 (CI 0.828 – 0.993, p <
0.001), and for DMSI was 0.980 (CI 0.899 – 0.996, p < 0.001)
suggesting excellent reliability for all measurements. The inter-reader
variability for MVACEQ was 13%, mean TMPG was 14%, and
DMSI was 7%.
Survival and mortality data were available for all subjects in the DMS
group. 27 ±18 months of follow-up was available after the
echocardiography study used for study enrollment. The all-cause
mortality rate was 53% in the DMS group and 41% in the RMS group at an
average survival duration of 13 ± 14 vs. 34±14 months after the
enrolment echocardiography. The Cox hazard regression model revealed
that the left atrial volume index and ESRD were independent predictors
of mortality in patients with DMS. Kaplan-Meier curve analysis showed a
non-significant trend towards worse survival when the cutoff values of
MVACEQ ≤ 1.0 cm2 and DMSI ≤ 0.35 were
used (Figure 5 ). Other echocardiographic parameters such as
MVACEQ ≤ 1.5 cm2, mean TMPG
> 7 mmHg, or SV index ≤ 0.35 did not predict mortality
risk.